Inhibition of cell division induced by external guide sequences (EGS Technology) targeting ftsZ

EGS (external guide sequence) technology is a promising approach to designing new antibiotics. EGSs are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. The ftsZ mRNA secondary structure was modeled and EGSs compleme...

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Bibliographic Details
Published in:PloS one 2012-10, Vol.7 (10), p.e47690
Main Authors: Sala, Carol Davies, Soler-Bistué, Alfonso J C, Korprapun, Leeann, Zorreguieta, Angeles, Tolmasky, Marcelo E
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Antibiotics
Antimicrobial agents
Antisense oligonucleotides
Antisense RNA
Bacterial Proteins - metabolism
Base Sequence
Biology
Biotechnology
Cell division
Cell Division - drug effects
Cleavage
Cloning
Cytoskeletal Proteins - metabolism
Deoxyribonucleic acid
DNA
Drug Design
E coli
Electrophoretic Mobility Shift Assay
Escherichia coli
Filaments
Genes
Inhibition
Ligands
Mathematics
Microscopy, Confocal
Molecular Sequence Data
mRNA
Nucleic Acid Conformation
Oligoribonucleotides, Antisense - pharmacology
Peptides
Plasmids
Promoter Regions, Genetic - genetics
Protein structure
Proteins
Ribonuclease A
Ribonuclease P
Ribonuclease P - metabolism
Ribonucleic acid
RNA
RNA Cleavage - drug effects
Science
Secondary structure
Staphylococcus infections
Studies
Technology
Terminator Regions, Genetic - genetics
tRNA
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Summary:EGS (external guide sequence) technology is a promising approach to designing new antibiotics. EGSs are short antisense oligoribonucleotides that induce RNase P-mediated cleavage of a target RNA by forming a precursor tRNA-like complex. The ftsZ mRNA secondary structure was modeled and EGSs complementary to two regions with high probability of being suitable targets were designed. In vitro reactions showed that EGSs targeting these regions bound ftsZ mRNA and elicited RNase P-mediated cleavage of ftsZ mRNA. A recombinant plasmid, pEGSb1, coding for an EGS that targets region "b" under the control of the T7 promoter was generated. Upon introduction of this plasmid into Escherichia coli BL21(DE3)(pLysS) the transformant strain formed filaments when expression of the EGS was induced. Concomitantly, E. coli harboring pEGSb1 showed a modest but significant inhibition of growth when synthesis of the EGSb1 was induced. Our results indicate that EGS technology could be a viable strategy to generate new antimicrobials targeting ftsZ.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0047690